Brain cancer patients who get radiation treatments often report debilitating fatigue, which is a subjective feeling of exhaustion that is not alleviated by rest or sleep, as a most common and distressing side effect of therapy. Cancer patients with fatigue also often report clusters of symptoms, including depression, cognitive impairment, and pain. The purpose is to produce a mouse model of radiation therapy for brain cancer and to examine resulting fatigue-related behaviors. In our planned experiments, the mouse model will allow controlled testing and measurements that are not possible in human subjects. With this model we may be able to dissociate changes in biology and behavior caused by direct exposure of the brain to radiation. We wish to determine if there is a dose-response relationship in cranial irradiation-induced fatigue as measured by voluntary wheel running and determine other behavioral correlates of fatigue such as cognition, strength, and cardiopulmonary function. Several studies in human clinical trials indicate that the occurrence of specific genetic polymorphism variations may leave patients more susceptible to severe fatigue during radiation treatment than others. We eventually want to determine the impact of these polymorphisms on occurrence and severity of fatigue with cranial irradiation. Alterations in circadian rhythm function and the presence of neuroinflammation have also been reported in concurrence with fatigue after cranial irradiation. In future, we also want to look at the behavioral and physiological impact of cranial irradiation on tumor-bearing animals. this study will investigate whether changes in activities of mice after irradiation are associated with changes in other behavioral measures, including: alternative measures of fatigue, depression-and anxiety-related behaviors, reward pathways, and skeletal muscle and cardiopulmonary function. This study will also associate biochemical changes with fatigue-related behavior using both pharmacological intervention and biochemical measurements from blood and tissue.